Understanding how the human immunodeficiency virus (HIV) fuses with its target cells is important for prevention and treatment of acquired immunodeficiency syndrome (AIDS). It is now known that two glycoproteins, gp41 and gp120, on HIV interact with a CD4 receptor and a chemokine coreceptor on the target cells to initiate the fusion process. Previously, we reported the finding that the N-terminal fusion peptide of gp41 can serve as a rather specific carrier to deliver a reporter peptide into cells susceptible to HIV infection. The cellular entry of the fusion peptide requires the presence of a chemokine receptor, such as CXCR4, CCR5, CCR6, and STRL 33. Immunofluorescence methods were used to demonstrate entry of the fusion peptide into cells, such as HeLa, Jurkat, MOLT-3, and 293 cells, containing one of the above-mentioned chemokine receptors. In the past year, we concentrated on showing that cells which do not contain these chemokine receptors and therefore are impermeable to the fusion peptide can be made permeable by permanently or transiently expressing a chemokine receptor in the cells. Expression of CCR6 and STRL 33 on Viro cells converted the cells into a form permeable to the fusion peptide. Since CCR6 and STRL 33 are not the major coreceptors involved in HIV cell fusion, we have started to express the main coreceptors, CXCR4 and CCR5, onto Viro cells, which are not susceptible to HIV infection. The work is in progress, but has yet to be completed. The evidence we have compiled so far, however, indicates that the fusion peptide utilizes the chemokine receptor as its point of entry into the cells.